Looking Beyond LDL-Cholesterol - A Study on Extended Lipid Profile in Indian Patients with Acute Coronary Syndrome

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Inter nal Medicine Section

Looking Beyond LDL-Cholesterol - A Study

on Extended Lipid Profile in Indian Patients

with Acute Coronary Syndrome

IntrOductIOn

Cardiovascular disease is a major cause of morbidity and mortality in India and dyslipidemia is considered one of the major risk factors [1]. Traditionally this includes elevated Low Density Lipoprotein Cholesterol (LDL-C), reduced High Density Lipoprotein Cholesterol (HDL-C) and elevated Total Cholesterol (TC) and Triglyceride (TGL) levels. The mainstay of treatment of dyslipidemia is aimed at reducing LDL-C levels [2]. The current National Cholesterol Education Program Adult Treatment Panel-III guidelines recommend target LDL-C levels of <70 mg/dL for statin treatment in patients with Acute Coronary Syndrome (ACS) [3]. But despite achieving the target LDL-C goal of <70 mg/dL with high intensity statins, there still remains a risk for future coronary events [4]. This could be explained by other co-morbid conditions like diabetes mellitus, hypertension, smoking, physical inactivity and genetic predisposition to recurrent events. However, there could be dyslipidemic risk beyond what the standard lipid profile consisting of TC, TGL, LDL-C, and HDL-C portrays. An extended lipid profile that looks at other lipid parameters such as Non-High Density Lipoprotein Cholesterol (non-HDL-C), Apolipoprotein-A1 (Apo-A1) and Apolipoprotein-B (Apo-B) and ratios derived from lipid parameters (TC/HDL-C and Apo-B/Apo-A1) may better reflect the dyslipidemic riskfor coronary events [4].

This study is an effort in this direction where we studied the prevalence and pattern of atherogenic dyslipidemia using a wider range of parameters than the standard lipid profile in statin naïve Indian patients presenting with an acute coronary syndrome, as data with this regard is limited.

MAterIAls And MethOds

This single-centre, prospective, observational study was conducted in the department of cardiology of a tertiary care teaching institute

in India. The study protocol was approved by the institutional review and ethics board (letter no- 10790/17). Written informed consent was obtained from all patients, as well as postal address and mobile telephone number. The study was conducted over a 7-month period from April to October 2017. Follow-up of the patients was done after 11 to 18 months (14-months average), with each patient receiving a phone call, text message and post card when follow-up was due. The diagnosis of myocardial infarction (MI) was made based on the universal definition of the same [5].

Inclusion criteria

Patients presenting to the Chest Pain Unit diagnosed as ACS, of more than 18 years of age, who were not on prior statin therapy, and with no contra-indications to high-intensity statin treatment, were included in the study.

exclusion criteria

Peri-procedural MI, pregnant women, inability to provide informed consent, patients with known history of thyroid, hepatic, or malignant disease and anemia were excluded.

All the patients presenting with acute coronary syndrome were given 80 mg atorvastatin loading dose, followed by 40 mg atorvastatin once daily. The patients were divided into 2 groups based on the follow-up obtained after statin therapy. Blood samples were taken within the first 24 hours of admission that included the standard lipid profile as well as Apo-B and Apo-A1 levels. Lipid profiles were measured using the cholesterol oxidase peroxidase method and apolipoprotein levels using the ELISA technique (Quantikine solid phase sandwich ELISA kit no- 1345/17). Non-HDL-C levels were obtained using the formula: Non-HDL-C=Total Cholesterol-HDL-C. Lipid parameters were considered abnormal if the values fell outside the following threshold points: TC >200 mg/dL, TGL >150 mg/dL, HDL-C <35 mg/dL, LDL-C >100 mg/dL, non-HDL-C >130 mg/dL, NAVEEN KUMAR1_{, LIJO VARGHESE}2_{, SUJITH THOMAS CHACKO}3_{, REKHA KARUPPUSAMI}4_{, ARUN JOSE}5_{, GEORGE JOSEPH}6

Keywords:

Apolipoprotein b, Apolipoprotein a1, Dyslipidemia, Myocardial infarction

ABstrAct

Introduction: Assessment of dyslipidemia with only Total Cholesterol (TC), Triglyceride (TGL), Low- and High-Density Lipoprotein Cholesterol (LDL-C, HDL-C) levels, Standard Lipid Profile (SLP), leads to under-estimation of dyslipidemia as a risk factor in Acute Coronary Syndrome (ACS).

Aim: To assess whether extended lipid profile gives a better risk assessment in ACS patients.

Materials and Methods: In this single-centre, prospective, observational study of statin-naïve patients presenting with ACS, SLP and Extended Lipid Profile (ELP), consisting of TC/ HDL-C ratio, non-HDL-C, apolipoprotein-B, apolipoprotein-A1 and their ratio, were studied at baseline and after high-intensity statin therapy. For continuous data, descriptive statistics mean±standard deviation and also 25th_-75th_{percentile was}

reported. Number of patients and percentages were reported

for categorical data. Pearson correlation coefficient was used to find the relationship between continuous variables.

results: In the present study, 139 patients (mean age 55 years, range 21-88 years, 78% male) presented with ACS: ST-Elevation Myocardial Infarction (STEMI) 79%, non-STEMI 17%, Unstable Angina (UA) 4%. The ELP (barring non-HDL-C) showed more dyslipidemia than SLP. Dyslipidemia declined across the age spectrum from young to old and worsened across the ACS spectrum from UA to STEMI. High-intensity statin therapy reduced LDL-C significantly but not to target levels in most patients.

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TC/HDL-C ratio >4, Apo-B >125 mg/dL and Apo-A1 <120 mg/dL Apo-B/Apo-A1 ratio >0.7 [6].

stAtIstIcAl AnAlysIs

For continuous data, descriptive statistics mean±standard deviation and also 25th_-75th_{percentile was reported. Number of patients and} percentages were reported for categorical data. Pearson correlation coefficient was used to find the relationship between continuous variables. For graphical representation, bar and scatter plots were used. All analyses were done using Statistical Package for Social Services software version 21.0 (Armonk, NY: IBM Corporation).

results

One hundred and thirty-nine patients with ACS were enrolled in this study. The clinical presentation of patients is shown in [Table/Fig-1]. There was a marked male preponderance (78%). The average age at presentation was 55 years with a wide range from 21 to 88 years. The most common presentation was ST-Elevation Myocardial Infarction (STEMI) seen in 79%, followed by Non-ST Elevation Myocardial Infarction (NSTEMI) seen in 17% and Unstable Angina (UA) seen in 4%. Younger males had a greater proportion of STEMI compared to older patients, the highest proportion (92%) being in males between 20 and 40 years of age [Table/Fig-2].

Age (years)

Men (n=109) Women (n=30)

STEMI NSTE-ACS Total STEMI NSTE-ACS Total

≤50 29 (88) 4 (12) 33 (100) 2 (67) 1 (33) 3 (100)

>50 59 (78) 17 (22) 76 (100) 19 (70) 8 (30) 27 (100)

Total 88 (81) 21 (19) 109 (100) 21 (70) 9 (30) 30 (100)

[table/Fig-1]: Clinical presentation of patients (n = 139).

STEMI: ST-elevation myocardial infarction; NSTE-ACS: Non-ST-elevation acute coronary syndrome (includes both unstable angina and non-ST-elevation myocardial infarction); Data are number (percentage) unless specified otherwise

Age (years)

Men

STEMI NSTE-ACS Total

20-40 11 (92) 1 (8) 12 (100)

41-60 45 (80) 11 (20) 56 (100)

>60 32 (78) 9 (22) 41 (100)

Total 88 (81) 21 (19) 109 (100)

[table/Fig-2]: Age specific acute coronary syndrome pattern in men. STEMI: ST-elevation myocardial infarction; NSTE-ACS: Non-ST-elevation acute coronary syndrome (includes both unstable angina and non-ST-elevation myocardial infarction); Data are number (percentage) unless specified otherwise

Females presenting with ACS were mostly above 50 years of age (post-menopausal), and had a higher proportion of non-ST elevation ACS (NSTE-ACS), which is the combination of UA and NSTEMI. [Table/Fig-3] shows baseline lipid profile patterns in men and women in the study. Both the standard and extended lipid profiles were not significantly different between both genders. This table also compares these parameters in patients who were re-assessed after statin therapy (Group 1) and those who were not (Group 2). The prevalence of dyslipidemia using specific thresholds for each of the parameters in the standard and extended lipid profiles are depicted in [Table/Fig-4,5]. LDL-C showed the highest proportion of abnormality in the standard lipid profile (using a threshold value of 100 mg/dL). Non-HDL-C did not show as much dyslipidemia (threshold value 130 mg/dL). The rest of the extended lipid profile, however, showed greater prevalence of dyslipidemia than LDL-C, Apo-B (threshold value 125 mg/dL) showing the most dyslipidemia. Even when patients with low/normal LDL-C are selected, all the extended lipid profile parameters were able to detect dyslipidemia in a significant proportion of patients [Table/Fig-6].

A striking feature seen in the standard lipid profile and in TC/HDL-C ratio, non-HDL-C and Apo-B patterns is the progressive reduction in dyslipidemia from the youngest age group (who had the worst

Variables

All patients (n=139)

Group 1 (n=53) (Follow-up obtained after statin therapy)

Group 2 (n=86) (No follow-up

obtained)

Age (years) 57±12 57±12 57±12

Male sex 109 (78%) 44 (83%) 65 (76%)

STEMI 109 (79%) 42 (79%) 67 (78%)

Smoking 49 (35%) 22 (42%) 27 (31%)

Diabetes mellitus 71 (50%) 25 (47%) 46 (53%)

Systemic hypertension 67 (48%) 25 (47%) 42 (49%)

Total cholesterol (mg/dL) 175±45 179±90 178±48

Triglycerides (mg/dL) 178±119 162±79 181±138

LDL-cholesterol (mg/dL) 120±41 123±35 119±45

HDL-cholesterol (mg/dL) 38±11 39±12 37±9

TC/HDL-cholesterol ratio 4.99±1.63 4.98±1.57 5.04±1.69

non-HDL-cholesterol (mg/dL) 140±45 140±38 141±49

Apo-AI (mg/dL) 111±114 117±32 116±19

Apo-B (mg/dL) 104±35 107±37 102±34

Apo-B/Apo-A1 ratio 0.95±0.29 0.94±0.26 0.95±0.33

[table/Fig-3]: Baseline characteristics of patients.

STEMI: ST-elevation myocardial infarction; LDL: Low density lipoprotein; HDL: High density lipoprotein; TC: Total cholesterol; Apo-A1: Apolipoprotein A1; Apo-B: Apolipoprotein B; Data are mean±standard deviation or number (percentage), There were no statistically significant differences between groups 1 and 2

[table/Fig-4]: Standard and extended lipid profile parameters at baseline in men and women.

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effect of high-intensity statins on lipid Profile

In patients who were re-assessed after 11-18 months of high-intensity statin therapy (Group 1 in [Table/Fig-3], there was highly statistically significant improvement in three of the four standard lipid profile parameters as well as TC/HDL-C ratio and non-HDL-C [Table/Fig-10]. Changes seen in non-HDL-C and apolipoprotein parameters were however not significant. Group 1 patients (n=53), who came for follow-up, did not differ significantly in baseline

Lipid parameter LDL-C <100 mg/dL (n=42) LDL-C <130 mg/dL (n=90)

Non-HDL-C >130 mg/dL 4 (10%) 34 (38%)

TC/HDL-C ratio >4 17 (40%) 54 (60%)

Apo-B >125 mg/dL 3 (7%) 11 (12%)

Apo-A1 <120 mg/dL 35 (83%) 73 (81%)

Apo-B/Apo-A1 ratio >0.7 26 (62%) 70 (78%)

Apo-B/Apo-A1 ratio >0.9 12 (9%) 41 (46%)

[table/Fig-6]: Dyslipidemia detected by the ELP in patients with low/normal LDL-C. LDL-C: Low density lipoprotein cholesterol; non-HDL-C: Non-high density lipoprotein cholesterol; TC/HDL-C: Total cholesterol/high density lipoprotein cholesterol; Apo-B: Apolipoprotein B; Apo-A1: Apolipoprotein A1; Data are number (percentage)

Age group

(years) 21-40 41-60 >60

Number of

patients 13 73 53

TC (mg/dL) 187±42 (151-226) 180±45 (152-210) 174±45 (144-198)

TGL (mg/dL) 219±133 (118-320) 172±122 (108-194) 166±114 (93-206)

HDL-C (mg/dL) 36±10 (28-43) 37±12 (30-44) 39±10 (33-42)

LDL-C (mg/dL) 126±38 (99-157) 121±46 (92-149) 114±35 (92-136)

TC/HDL-Cratio 5.6±2 (3.7-6.8) 5±2 (4-6.4) 4.6±1.3 (3.7-5.5)

non-HDL-C

(mg/dL) 151±43 (118-188) 143±46 (112-168) 135±43 (105-161)

Apo-B (mg/dL) 119±38 (83-161) 109 ±38 (84-125) 93±26 (72-110)

Apo-AI (mg/dL) 121±26 (104-142) 113 ±28 (96-122) 107±23 (92-119) Apo-B/Apo-AI

ratio 0.9±0.4 (0.7-1.1) 1±0.3 (0.8-1.1) 0.9±0.2 (0.7-1.1)

[table/Fig-7]: Baseline lipid profiles according to age categories.

TC: Total cholesterol; TGL: Triglyderides; HDL-C: High density lipoprotein cholesterol; LDL-C: Low density lipoprotein cholesterol; Apo-B: Apolipoprotein B; Apo-A1: Apolipoprotein A1; Data are mean±standard deviation (interquartile range); unless specified otherwise

Statistic Mean SD Median IQR p-value

TC (mg/dL)

Baseline 179 90 177 116-269

0.000*

After 140 39 129 110-198

Change 39 51 46 6-73

TGL (mg/dL)

Baseline 162 79 145 42-249

0.022*

After 138 63 15 67-196

Change 24 74 130 -25-55

HDL-C (mg/dL)

Baseline 39 12 37 17-67

0.081

After 36 9 36 21-76

Change 3 11 1 -4-9

LDL-C (mg/dL)

Baseline 123 35 45 26-220

0.000*

After 92 39 84 26.5-288

Change 31 49 39 -0.5-68

Non-HDL-C (mg/dL)

Baseline 140 38 143 41-220

0.000*

After 104 39 99 32-149

Change 36 50 39 9-71

TC/HDL-C ratio

Baseline 4.98 1.57 4.74 1.5-6.9

0.000*

After 4.02 1.26 3.91 1.6-8

Change 0.96 1.54 0.96 -0.2-2.1

Apo-B (mg/dL)

Baseline 107 37 102 54-159

0.41

After 109 39 105 71-176

Change -2 48 -3 -17-17

Apo-AI (mg/dL)

Baseline 117 32 107 64-266

0.53

After 116 19 115 85-283

Change 1 33 -4 -21-14

Apo-B/Apo-AI ratio

Baseline 0.94 0.26 0.94 0.8-1.1

0.68

After 0.92 0.37 0.90 0.7-1.1

Change 0.02 -0.11 0.04 -0.2-0.2

[table/Fig-10]: Change in lipid profile after statin therapy in all patients with follow-up (n=53).

SD: Standard deviation; IQR: Interquartile range; TC: Total cholesterol; TGL: Triglycerides; HDL-C: High density lipoprotein cholesterol; LDL-C: Low density lipoprotein cholesterol; Apo-B: Apolipoprotein B; Apo-A1: Apolipoprotein A1; P values represent significance of difference in mean in each category; *statistically significant

[table/Fig-9]: Correlation of lipid profile parameter levels and ratios with corresponding apolipoprotein levels and ratios.

UA (n=6) Median

(25th_{, 75}th₎

NSTEMI (n=24)

Mean (SD) STEMI (n=109) Mean (SD)

ApoAI (mg/dL) 115.50 (106.75, 142.25) 108.96 (24.35) 108.0 (5)

ApoB (mg/dL) 70.5 (52.5, 115) 104.8 (39.7) 104.5 (33.5)

TGL (mg/dL) 74 (40.5, 189) 168.6 (86.5) 142.0 (35)

LDL (mg/dL) 82.5 (67.25, 138.25) 115.2 (46.9) 121.09 (39.9)

TC (mg/dL) 138.5 (123.25, 199.25) 177.2 (53.2) 179.4 (42.2)

HDL (mg/dL) 38.5 (32.75, 67) 40.1 (11.7) 36.9 (9.5)

TC/HDL 3.05 (2.5, 6.7) 4.7 (2.06) 5.09 (1.49)

Non HDL (mg/dL) 102 (66.75, 142) 37.08 (55) 142.5 (41.4)

ApoB/ApoAI 0.63 (0.49, 0.8) 0.99 (0.40) (0.26)

[table/Fig-8]: Baseline standard and extended lipid profile across ACS spectrum. TC: Total cholesterol; TGL: Triglyderides; HDL-C: High density lipoprotein cholesterol; LDL-C: Low density lipoprotein cholesterol; Apo-B: Apolipoprotein B; Apo-A1: Apolipoprotein A1; Data are mean±standard deviation (interquartile range), unless specified otherwise

dyslipidemia) to the oldest age group in each of these parameters [Table/Fig-7]. Apo-A1 values, on the other hand, declined (worsened) as age increased, and the Apo-B/Apo-A1 ratio consequently remained essentially unchanged.

[Table/Fig-8] shows the pattern of standard and extended lipid profile across the ACS spectrum from UA to STEMI. There was progressive worsening of all four standard lipid profile parameters as well as the TC/HDL-C ratio and non-HDL-C across the spectrum. The mean LDL levels rose from 98 mg/dL in the UA group to 115 mg/dL in the NSTEMI group and 121 mg/dL in the STEMI group. The apolipoprotein parameters however did not show this worsening trend.

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Age group 21-40 years (n=5)

TC (mg/dL)

Baseline 171 43 157 134-214

0.14

After 133 18 142 114-146

Change 38 10 46 6-73

TGL (mg/dL)

Baseline 188 94 131 117-288

0.14

After 145 39 114 127-185

Change 43 14 56 -1-103

HDL-C (mg/dL)

Baseline 34 11 30 27-43

0.6

After 31 5 33 27-34

Change 3 10 0 -3-10

LDL-C (mg/dL)

Baseline 117 40 105 85-156

0.7

After 106 34 94 82-136

Change 11 39 49 -52-70

TC (mg/dL)

Baseline 182 36 188 167-210

0.001*

After 138 49 131 117-164

Change 44 51 36 1-71

TGL (mg/dL)

Baseline 154 57 150 102-194

0.29

After 140 61 137 99-170

Change 14 63 13 -28-49

HDL-C (mg/dL)

Baseline 38 13 36 28-45

0.43

After 37 9 35 30-43

Change 1 11 1 -5-8

LDL-C (mg/dL)

Baseline 125 39 129 101-148

0.002*

After 91 38 83 67-106

Change 34 47 37 -2-69

Age group >60 years (n=21)

TC (mg/dL)

Baseline 177 43 175 159-198

0.01*

After 139 46 126 111-146

Change 38 54 46 17-68

TGL (mg/dL)

Baseline 166 99 145 94-211

0.36

After 133 71 122 91-149

Change 33 92 15 -44-83

HDL-C (mg/dL)

Baseline 40 11 38 33-44

0.19

After 36 8 37 30-42

Change 4 13 2 -4-12

LDL-C (mg/dL)

Baseline 122 29 119 99-137

0.02*

After 91 42 83 59-102

Change 31 49 45 13-60

[table/Fig-11]: Change in standard lipid profile after statin therapy in different age categories.

SD: Standard deviation; IQR: Interquartile range; TC: Total cholesterol; TGL: Triglyderides; HDL-C: High density lipoprotein cholesterol; LDL-C: Low density lipoprotein cholesterol; Apo-B: Apolipoprotein B; Apo-A1: Apolipoprotein A1; p values represent significance of difference in mean in each category; *statistically significant

non-HDL-C (mg/dL)

Baseline 137 44 127 103-177

0.14

After 102 19 107 83-119

Change 35 49 41 -6-70

TC/HDL-C ratio

Baseline 5.5 2.4 5 3.8-7.4

0.14

After 4.4 1.2 4.1 3.6-5.4

Change 1.1 1.5 0.9 0.3-2.4

Apo-B (mg/dL)

Baseline 105 41 107 70-139

0.69

After 115 13 112 103-128

Change -10 35 -4 -44-21

Apo-AI (mg/dL)

Baseline 116 26 111 93-142

0.35

After 103 11 108 91-112

Change 13 31 7 -10-40

Apo-B/Apo-AI ratio

Baseline 0.88 0.16 0.83 0.74-1.04

0.10

After 0.91 0.19 0.96 0.71-1.08

Change -0.03 0.25 -0.12 0.05-0.27

non-HDL-C (mg/dL)

Baseline 140 39 143 111-167

0.002*

After 104 39 99 79-126

Change 36 51 41 15-67

TC/HDL-C ratio

Baseline 5.2 1.5 4.8 4.3-6.4

0.002*

After 4.1 1.5 3.9 1.5-4.5

Change 1.1 1.5 0.9 -0.3-2.4

Apo-B (mg/dL)

Baseline 115 44 106 95-134

0.98

After 107 39 106 78-127

Change 8 50 -3 -13-21

Apo-AI (mg/dL)

Baseline 118 38 107 96-134

0.39

After 117 20 118 108-127

Change 1 40 -8 -26-18

Apo-B/Apo-AI ratio

Baseline 0.99 0.26 0.97 0.8-1.1

0.5

After 0.93 0.44 0.91 0.6-1

Change 0.06 0.43 0.04 0.2-0.7

Age group >60 years (n=21)

non-HDL-C (mg/dL)

Baseline 137 41 129 115-159

0.01*

After 103 42 92 76-109

Change 34 51 39 15-67

TC/HDL-C ratio

Baseline 4.2 1.4 4.7 3.3-5.4

0.04*

After 3.8 0.9 3.6 3-4.6

Change 0.8 1.5 1.1 -0.5-2.2

Apo-B (mg/dL)

Baseline 99 21 97 82-110

0.41

After 111 44 106 81-126

Change -12 46 -3 -13-21

Apo-AI (mg/dL)

Baseline 115 26 106 95-136

0.45

After 118 19 115 101-136

Change -3 23 -7 -21-10

Apo-B/Apo-AI ratio

Baseline 0.89 0.25 0.89 0.69-1.05

2.09

After 0.95 0.39 0.90 0.68-1.09

Change -0.06 0.36 0.05 0.21-0.68

[table/Fig-12]: Change in extended lipid profile after statin therapy in different age categories.

SD: Standard deviation; IQR: Interquartile range; TC: Total cholesterol; TGL: Triglycerides; HDL-C: High density lipoprotein cholesterol; LDL-C: Low density lipoprotein cholesterol; Apo-B: Apolipoprotein B; Apo-A1: Apolipoprotein A1; p values represent significance of difference in mean in each category; *statistically significant

characteristics from Group 2 patients (n=86), who did not return for follow-up; there were 10 interim deaths in the Group 2. As shown in [Table/Fig-11,12], in the 41-60 and >60 year age categories, significant improvement was seen at follow-up in TC, LDL-C, non-HDL-C and TC/non-HDL-C; the small number of patients in the 21-40 year age category probably led to the changes being insignificant in this category.

women in the INTERHEART study [7,8]. Consistent evidence from multiple genetic, epidemiological and clinical studies firmly

dIscussIOn

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establishes that LDL-C causes atherosclerotic vascular disease [9]. However, LDL-C alone, or even the standard lipid profile, may be insufficient to adequately represent the dyslipidemic risk, and other lipid parameters need to be looked at. In this study we examined the patterns of atherogenic dyslipidemia prevalent in Indian patients presenting with ACS using the standard and an extended lipid profile, both at initial presentation and after statin therapy. A number of significant findings emerged, many of which corroborate with earlier studies, and some which may have important diagnostic and therapeutic implications.

The first is that the standard lipid profile is insufficient to expose the total dyslipidemic risk in patients. This is demonstrated by the fact that the proportion of patients with abnormality in several of the extended lipid profile parameters was more than the proportion with elevated LDL-C [Table/Fig-5] and that several of the extended lipid profile parameters were abnormal in patients with low/normal LDL-C. These findings corroborate earlier studies that have looked at extended lipid profile parameters. Liu et al demonstrated a strong association between non-HDL-C and cardiovascular risk, independent of the LDL-C levels [9]. Non-HDL-C, measures the cholesterol content present in all the atherogenic lipoproteins. It has also been shown to be a good risk predictor in patients with ACS. In the emerging risk factors collaboration, a combined data analysis from 68 studies, the authors report that non-HDL-C was the best predictor for coronary artery disease events and for strokes [10]. The Incremental Decrease in End Points through Aggressive Lipid Lowering (IDEAL) trial showed that elevated non-HDL-C and Apo-B levels were the best predictors of adverse cardiovascular outcomes in patients who were on lipid-lowering therapy, and when Apo-B or non-HDL-C was included in the regression model, LDL-C was not associated with poor outcomes [11].

In the current study, the apolipoprotein parameters and the TC/ HDL-C ratio showed greater abnormality than non-HDL-C in ACS patients. Apo-B is the primary apolipoprotein of chylomicrons, very low-, intermediate- and low-density lipoprotein particles, whereas Apo-A1 constitutes approximately 70% of the apolipoprotein in HDL-C particles. Therefore Apo-B is reflective of total atherogenic potential whereas ApoA-1 reflects anti-atherogenic capabilities. High Apo-B/Apo-A1 ratio causes more cholesterol to be deposited in the arterial wall, promoting atherogenesis and increasing cardiovascular risk. High Apo-B/Apo-A1 ratio increased the risk of myocardial infarction in the AMORIS [12] and INTERHEART [8] studies. Apo-B/ Apo-A1 ratio was found to be a better risk predictor than LDL-C in the prospective MONICA/KORA study [13]. Goswami et al also suggested that Apo-B/Apo-A1 ratio is a better discriminator of coronary artery disease risk in the atherosclerosis prone Indians [14]. Based on results from AMORIS and INTERHEART studies, patients can be risk stratified for the development of MI, based on Apo-B/Apo-A1 ratio: ratios of <0.3 (women) and 0.4 (men) as low risk; 0.3-0.6 (women) and 0.4-0.7 (men) as medium risk and 0.8-1.0 (women) and 0.9-1.1 (men) as high risk.

The second significant finding in our study was that young patients presenting with ACS had worse dyslipidemic status compared to older patients. There was a consistent pattern of improving lipid profile parameters across the age spectrum from young to old; only the apolipoproteins did not show this trend. This suggests that dyslipidemia may be a more important risk factor in the younger age groups, whereas the other risk factors (and age itself) may contribute more to the overall risk in older patients. This is of great importance, given the high prevalence of cardiovascular diseases and acute coronary syndromes in young Indiansand that this is an economically productive age group. Prabhakaran D et al., in their epidemiological report of cardiovascular disease, noted that four persons die of MI every two minutes in India and the age group is mainly between 30 and 50 [15]. This would make this age group a special target for urgent preventive and corrective measures to reduce the risk of a future coronary event.

Another interesting trend seen in our study was the worsening of lipid profile parameters through the ACS spectrum from UA to NSTEMI to STEMI [Table/Fig-8]. All standard and extended lipid profile parameters (excepting the apolipoprotein parameters) showed this trend which may indicate that the worse the dyslipidemia, the more likely the ACS will be a STEMI. This pattern is consistent with the earlier finding that young patients who have the worst dyslipidemia mostly present with STEMI.

A notable negative finding in this study was the lack of gender difference in lipid profile parameters [Table/Fig-4]. In a population based study from Greece, Kolovou GD et al., reported gender differences among dyslipidemic patients-higher TC, lower TGL and lower TC/HDL ratios among women [16]. The relatively small number of women, contributing less than one-fourth of our study group, may have contributed to this lack of demonstrable gender difference. High-intensity statin therapy produced statistically highly significant improvements in lipid profile parameters [Table/Fig-10]; only HDL-C and the apolipoprotein parameters did not show significant change. However the LDL-C level achieved was still well above the desirable target of <70 mg/dL. The reasons for this include irregular intake of statin, reduction in dose by the patient or general practitioner and inadequacy of statin therapy alone in achieving target LDL-C levels. This shows the practical problems faced in risk reduction in the real world and the need for other lipid lowering therapies.

lIMItAtIOn

There are several limitations to this study. It was a single-centre, hospital-based, observational study done in a tier-3 city with patients drawn from semi-urban background that may not be truly representative of the general population in India. The number of patients in some sub-groups, such as women and NSTE-ACS were small. Other lipid parameters that could contribute to dyslipidemic risk were not studied such as lipoprotein (a) and small dense LDL-C.

cOnclusIOn

Dyslipidemia is an important risk factor in statin-naïve Indian patients who present with ACS. The extended lipid profile is better able to identify dyslipidemic risk than the standard lipid profile or LDL-C level alone. Dyslipidemia is more prevalent in young patients and those who present with STEMI, suggesting a greater role as a risk factor and indicating the need for more effective preventive measures in these patients. High-intensity statin therapy significantly improves lipid parameters in ACS patients, but achievement of target lipid levels remains practically elusive in most patients.

AcKnOwledgeMents

We sincerely thank the department of clinical biochemistry and the staff in chest pain unit cardiology for their contribution.

reFerences

Reddy SK, Shah B, Varghese C, Ramadoss A. Responding to the threat of

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(6)

PARTICULARS OF CONTRIBUTORS:

1. Assistant Professor, Department of Cardiology, Christian Medical College, Vellore, Tamil Nadu, India. 2. Associate Professor, Department of Cardiology, Christian Medical College, Vellore, Tamil Nadu, India. 3. Associate Professor, Department of Cardiology, Christian Medical College, Vellore, Tamil Nadu, India. 4. Lecturer, Department of Biostatistics, Christian Medical College, Vellore, Tamil Nadu, India. 5. Lecturer, Department of Clinical Biochemistry, Christian Medical College, Vellore, Tamil Nadu, India. 6 Professor, Department of Cardiology, Christian Medical College, Vellore, Tamil Nadu, India.

PLAGIARISM CHECKING METHODS: [Jain H et al.]

• Plagiarism X-checker: Aug 16, 2019 • Manual Googling: Aug 19, 2019 • iThenticate Software: Oct 03, 2019 (12%)

ETyMOLOGy: Author Origin

NAME, ADDRESS, E-MAIL ID OF THE CORRESPONDING AUTHOR:

Lijo Varghese,

Department of Cardiology, CMC Hospital, Vellore, Tamil Nadu, India. E-mail: [email protected]

Date of Submission: Aug 14, 2019

Date of Peer Review: Aug 21, 2019

Date of Acceptance: Sep 13, 2019

Date of Publishing: Nov 01, 2019

AUTHOR DECLARATION:

• Financial or Other Competing Interests: No

• Was Ethics Committee Approval obtained for this study? Yes

• Was informed consent obtained from the subjects involved in the study? Yes

• For any images presented appropriate consent has been obtained from the subjects. Yes

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